Evaluation of Mucoadhesive Tablets
Tablet dimensions:- The dimensions determined for formulated tablets were tabulated in Table No 2 Tablets mean thickness (n = 3) were uniform in F1 to F12 formulations and were found to be in the range of 0.32 cm to 0.345 cm.
Hardness:- The hardness of tablets of each batch ranged between 6.2 to 7.3 kg/cm2 (Table No 2). This ensures good handling characteristics for all batches.
Friability Test:- The values of friability test were tabulated in Table No 2. The Percentage friability was less than 1% in all the formulations(Except formulation F 6) ensuring that the tablets were mechanically stable.
Weight Variation Test:- The percentage weight variations for all formulations were tabulated in Table No 2. All the formulated (F1 to F12) tablets passed weight variation test as the % weight variation was within the standard pharmacopoeial limits of ±7.5% of the weight. The weights of all the tablets were found to be uniform with low standard deviation values.
Drug Content Uniformity:- The percentage of drug content for F1 to F12 was found to be between 99.05% and 100.94% of Clarithromycin, it complies with official specifications. The results were shown in Table No 2.
Table :2 Physical properties of tablets
Formulation No. | Hardness* (kg/cm2) | Thickness* (cm) | % Friability | Weight Variation*(mg) | % Drug content |
F 1 | 6.6 ± 0.152 | 0.325±.00110 | 0.52 | 453±2.08 | 100.41 |
F 2 | 6.8 ± 0.289 | 0.341 ± 0.0012 | 0.64 | 449 ± 1.52 | 100.94 |
F 3 | 6.3 ± 0.462 | 0.343 ± 0.0010 | 0.68 | 454 ± 4.93 | 99.52 |
F 4 | 7.3 ± 0.354 | 0.328 ± 0.0006 | 0.85 | 452 ± 5.29 | 100.94 |
F 5 | 6.9 ± 0.145 | 0.321 ± 0.0010 | 0.76 | 448 ± 3.21 | 99.11 |
F 6 | 6.8 ± 0.587 | 0.323 ± 0.0010 | 1.09 | 449 ± 4.00 | 99.52 |
F 7 | 6.7 ± 0.345 | 0.331 ± 0.0006 | 0.60 | 454 ± 2.64 | 101.82 |
F 8 | 6.8 ± 0.306 | 0.331 ± 0.0115 | 0.81 | 449 ± 4.04 | 99.05 |
F 9 | 7.3 ± 0.328 | 0.345 ± 0.0006 | 0.89 | 448 ± 1.52 | 101.41 |
F10 | 6.3 ± 0.133 | 0.337 ± 0.0029 | 0.82 | 451 ± 1.52 | 99.75 |
F 11 | 6.2 ± 0.218 | 0.332 ± 0,0012 | 0.83 | 451 ± 1.32 | 99.65 |
F 12 | 6.5 ± 0.314 | 0.332 ± 0.0009 | 0.86 | 453 ± 2.14 | 99.48 |
* (n = 3, ±S.D.) |
Mucoadhesive Force Measurement of Tablet
Adhesion was reported to be effected by hydration. Hydration of the mucoadhesive polymer is essential to initiate the mucoadhesive bonding process. In case of tablets applied in the dehydrated state, which is most convenient, it is essential that sufficient water is available so that rapid hydration takes place, and a flexible rubbery state occurs. The capillary force arises when water from the space between the mucosa and the polymer was taken up by a dry system. Once the bond is formed, reduction in the rate of swelling due to water uptake from the tissue surface may only prolong the association of the tablet with the mucosa. Removal of water from the underlying mucosa layer by the hydrating polymer may increase the cohesive forces of mucus; this plays a vital role in the establishment of an effective mucoadhesive bond.Modified balance method was used for the measurement of mucoadhesive force. During measurement of mucoadhesive force 15 min contact time was kept constant. Mucoadhesive force depends on the viscosity and concentration of the polymer. Formulation F1 was having lowest mucoadhesive force because the HPMC K4M having lower viscosity. While formulation (F 12) containing HPMC K15M and carbopol 971 shows higher mucoadhesion force due to higher viscosity .In order to increase the mucoadhesive strength of low viscosity polymer containing HPMC K4M was combined with carbopol 974P having good mucoadhesive property. This combination results in good mucoadhesive properties as shown in Table no. 7. From the above results it was found that polymers having high molecular weight and high viscosity exhibited higher adhesion. HPMC K15M and Carbopol 974P were found to be having good mucoadhesive strength. HPMC and carbopol possesses hydroxy and carboxy groups respectively required for bioadhesion.
Table. 3 Mucoadhesive strength and force of formulation F 1 to F 12
Formulation No | Mucoadhesive Strength (gm) | Mucoadhesion Force (dyne) |
F 1 | 10.45 ± 1.32 | 1.1243 |
F 2 | 11.89 ± 1.17 | 1.1664 |
F 3 | 18.93 ± 2.37 | 1.8570 |
F 4 | 22.89 ± 4.92 | 2.2455 |
F 5 | 26.78 ± 4.46 | 2.6271 |
F 6 | 34.27 ± 1.06 | 3.3618 |
F 7 | 31.69 ± 1.73 | 3.1087 |
F 8 | 37.43 ± 1.08 | 3.6718 |
F 9 | 38.46 ± 2.55 | 3.3772 |
F 10 | 36.93 ± 2.64 | 3.6228 |
F 11 | 42.37 ± 2.89 | 4.1564 |
F 12 | 46.48 ± 1.87 | 4.5596 |
Swelling Study of Tablets
Results showed that polymers with higher concentration had lower swelling this was due to the fact that polymers concentration restricts the movement of the polymers. (Table. 4)
Table 4
Percentage swelling of formulation F 1 to F 12
Form. no. | Time (hrs) |
1 | 2 | 3 | 4 | 5 | 6 | 7 | 8 | 10 |
F1 | 133.8 | 136.56 | 137.4 | 139.25 | 140.12 | 142.23 | 143.36 | 143.89 | 144.87 |
F2 | 98.95 | 134.32 | 135.6 | 136.85 | 137.64 | 139.74 | 140.61 | 143.58 | 144.34 |
F3 | 100.2 | 130.67 | 132.2 | 134.69 | 136.67 | 137.83 | 138.97 | 139.21 | 140.73 |
F4 | 63.36 | 96.83 | 100.9 | 105.36 | 111.86 | 119.34 | 125.87 | 130.94 | 134.99 |
F5 | 73.31 | 115.46 | 118.4 | 120.81 | 121.36 | 125.36 | 129.35 | 131.23 | 132.21 |
F6 | 79.66 | 113.57 | 115.6 | 116.25 | 117.49 | 119.39 | 125.75 | 128.37 | 129.99 |
F7 | 85.28 | 129.45 | 131.9 | 132.12 | 132.68 | 133.25 | 133.24 | 133.92 | 134.17 |
F8 | 98.28 | 129.15 | 30.57 | 132.69 | 133.24 | 134.53 | 135.45 | 136.57 | 137.51 |
F9 | 98.27 | 126.93 | 128.7 | 129.98 | 130.24 | 132.48 | 132.25 | 134.36 | 135.03 |
F10 | 52.36 | 83.45 | 87.36 | 95.36 | 102.23 | 106.35 | 115.23 | 118.63 | 122.48 |
F11 | 68.58 | 109.67 | 111.6 | 113.65 | 115.34 | 118.39 | 11934 | 123.35 | 125.68 |
F12 | 73.59 | 111.34 | 112.3 | 112.98 | 115.34 | 116.37 | 117.68 | 118.45 | 119.36 |
Formulations containing HPMC K 4 M i.e. F1, F2 and F3 had higher % Swelling than formulations containing HPMC K 15 M i.e. F4, F5 and F6. Polymers HPMC K4M and Carbopol 974P have higher cross linking indicate that polymers having cross linking constrain and therefore the polymer did not open up easily.
Fabergas and Gareia have reported a correlation between % Swelling and mucoadhesive strength. Initial swelling due to hydration aided bioadhesion but further swelling induced over-extension of hydrogen bonds and other forces. This resulted in lower bioadhesion.
% Swelling decreased with polymer concentration because high concentration of the polymer restricts its movement.
Comparison of In vitro release profile of optimized formulation F 9 and F 12 with market CR tablet (Biaxin)
In vitro release profile of optimized formulation F9 and F 12 were compared with marketed SR tablet (Biaxin-500). The Initial percentage drug release after 1 hour for F9, F12 and Biaxin were found to 15.25, 14.64 and 8.59 respectively. The percentage drug release after 12 hour for F9, F12 and Biaxin were found to 95.78, 96.38 and 85.32 respectively, so the release from the optimized formulation were higher compared to marketed product.
Table. : 5 Cumulative drug release of formulation F 9 and F 12
Time (Hour) | % Cumulative Drug Release* |
F 9 | F 12 | Biaxin Tablet |
1 | 15.25 ± 1.16 | 14.64 ± 1.96 | 8.59 ± 0.36 |
2 | 31.70 ± 3.48 | 32.97 ± 3.56 | 15.58 ± 0.63 |
3 | 40.95 ± 2.99 | 42.56 ± 1.34 | 27.94 ± 1.89 |
4 | 51.80 ± 1.17 | 53.30 ± 2.36 | 33.18 ± 2.92 |
5 | 59.88 ± 6.95 | 61.26 ± 4.96 | 46.51 ± 1.61 |
6 | 70.07 ± 8.37 | 72.57 ± 4.78 | 53.26 ± 0.85 |
7 | 78.97 ± 6.99 | 79.64 ± 5.26 | 61.52 ± 1.44 |
8 | 85.56 ± 3.28 | 86.97 ± 4.29 | 65.74 ± 0.31 |
10 | 91.81 ± 4.65 | 90.71 ± 3.67 | 78.83 ± 2.68 |
12 | 95.78 ± 0.95 | 96.38 ± 1.21 | 85.32 ± 1.30 |
* (n=3, ±S.D.)